066c02b7f6ba7182e5edadfc40706d5a 289530.pdf c79af106cc8a512a7aa1ac9c59c24d3351be9c73 289530.pdf 151d5d081dbc23bab27e29b3f175b9ee5d69783d9e9d6560f844f256e9e1770c 289530.pdf Title: Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment Subject: Background: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? Methods: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983–2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan–Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children’s survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. Results: ASRw 1983–2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983–2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983–1993, 4.3%^ (1.1; 7.7); 1993–2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983–2004: 2.9%^ (0.9; 4.9); 2004–2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991–2005), with no significant trends (except for non-malignant tumours). Conclusions: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours. Keywords: childhood CNS tumours; adolescent CNS tumours; incidence; survival; time trends; paediatric oncology; population-based cancer registries; Spain Author: Maria D. Chirlaque, Rafael Peris-Bonet, Antonia Sánchez, Ofelia Cruz, Rafael Marcos-Gragera, Gonzalo Gutiérrez-Ávila, José R. Quirós-García, Fernando Almela-Vich, Arantza López de Munain, Maria J. Sánchez, Paula Franch-Sureda, Eva Ardanaz, Jaume Galceran, Carmen Martos, Diego Salmerón, Gemma Gatta, Laura Botta, Adela Cañete and the Spanish Childhood Cancer Epidemiology Working Group Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Dec 19 09:28:52 2023 CET ModDate: Tue Dec 19 09:34:09 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 32 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5199464 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SDIDBK+VnURWPalladioL Type 1 Custom yes yes no 10 0 STXWEU+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ZFAOEK+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 TANCIS+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 FFAYKL+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 AHSHLD+CMSY10 Type 1 Builtin yes yes no 69 0 IKPNRE+VnURWPalladioL-Italic Type 1 Custom yes yes no 85 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 102 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 105 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 108 0 LLOLGG+PalatinoLinotype TrueType MacRoman yes yes no 111 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 126 0 LLOJKM+PalatinoLinotype CID TrueType Identity-H yes yes yes 129 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 135 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 138 0 LLOLGG+PalatinoLinotype TrueType MacRoman yes yes no 141 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 156 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 159 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 162 0 LLOLGG+PalatinoLinotype TrueType MacRoman yes yes no 165 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 179 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 182 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 185 0 LLOLGG+PalatinoLinotype TrueType MacRoman yes yes no 188 0 LLPDIH+Arial CID TrueType Identity-H yes yes yes 203 0 LLPDII+Arial,Bold CID TrueType Identity-H yes yes yes 209 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 215 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 218 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 221 0 LLPDIG+Arial,Italic TrueType WinAnsi yes yes no 224 0 LLPDIH+Arial CID TrueType Identity-H yes yes yes 237 0 LLPDII+Arial,Bold CID TrueType Identity-H yes yes yes 243 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 249 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 252 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 255 0 LLPDIG+Arial,Italic TrueType WinAnsi yes yes no 258 0 LLPDIH+Arial CID TrueType Identity-H yes yes yes 271 0 LLPDII+Arial,Bold CID TrueType Identity-H yes yes yes 277 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 283 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 286 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 289 0 LLPDIG+Arial,Italic TrueType WinAnsi yes yes no 292 0 LLPDIH+Arial CID TrueType Identity-H yes yes yes 305 0 LLPDII+Arial,Bold CID TrueType Identity-H yes yes yes 311 0 LLOJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 317 0 LLOJKN+PalatinoLinotype TrueType WinAnsi yes yes no 320 0 LLOJKP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 323 0 LLOLGG+PalatinoLinotype TrueType MacRoman yes yes no 326 0 LLPDIG+Arial,Italic TrueType WinAnsi yes yes no 329 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 340 0 BCDKEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 344 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 348 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 352 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 356 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 363 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 375 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 383 0 BCDKEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 387 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 391 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 395 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 399 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 406 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 428 0 BCDKEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 432 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 436 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 440 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 444 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 451 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 463 0 BCDKEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 467 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 471 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 475 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 479 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 486 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 493 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-02-29 02:34:20 CET RepresentationInformation: 289530.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-02-28 11:07:00 CET Size: 5199464 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 847 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Item: Title: Results Destination: section.3 Children: Item: Title: Incidence Destination: subsection.3.1 Item: Title: Incidence Rates Destination: subsection.3.2 Item: Title: Incidence Time Trends, 1983 2007 Destination: subsection.3.3 Item: Title: Survival Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Children: Item: Title: Incidence Destination: subsection.4.1 Item: Title: Survival Destination: subsection.4.2 Item: Title: Conclusions Destination: section.5 Item: Title: Appendix A Destination: section.A. Item: Title: References Destination: section.A. Info: Title: Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment Author: Maria D. Chirlaque, Rafael Peris-Bonet, Antonia Sánchez, Ofelia Cruz, Rafael Marcos-Gragera, Gonzalo Gutiérrez-Ávila, José R. Quirós-García, Fernando Almela-Vich, Arantza López de Munain, Maria J. Sánchez, Paula Franch-Sureda, Eva Ardanaz, Jaume Galceran, Carmen Martos, Diego Salmerón, Gemma Gatta, Laura Botta, Adela Cañete and the Spanish Childhood Cancer Epidemiology Working Group Subject: Background: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? Methods: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983 2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children’s survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. Results: ASRw 1983 2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983 2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983 1993, 4.3%^ (1.1; 7.7); 1993 2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983 2004: 2.9%^ (0.9; 4.9); 2004 2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991 2005), with no significant trends (except for non-malignant tumours). Conclusions: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours. Keywords: childhood CNS tumours; adolescent CNS tumours; incidence; survival; time trends; paediatric oncology; population-based cancer registries; Spain Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Dec 19 09:28:52 CET 2023 ModDate: Tue Dec 19 09:34:09 CET 2023 ID: 0x6796cb2d90ed55592ad986ba0e5722dd, 0x6796cb2d90ed55592ad986ba0e5722dd Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ZFAOEK+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: ZFAOEK+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: AHSHLD+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: AHSHLD+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: IKPNRE+VnURWPalladioL-Italic FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: IKPNRE+VnURWPalladioL-Italic Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: TANCIS+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: TANCIS+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: SDIDBK+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: SDIDBK+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FFAYKL+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: FFAYKL+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: STXWEU+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: STXWEU+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 54, 279, 152, 288 Annotation: Subtype: Link Rect: 34, 269, 87, 276 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 152, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 246, 644, 257, 657 Annotation: Subtype: Link Rect: 173, 631, 184, 645 Annotation: Subtype: Link Rect: 163, 618, 174, 632 Annotation: Subtype: Link Rect: 281, 618, 292, 632 Annotation: Subtype: Link Rect: 327, 606, 338, 620 Annotation: Subtype: Link Rect: 306, 77, 315, 87 ActionDest: 526 Annotation: Subtype: Link Rect: 114, 17, 265, 28 Annotation: Subtype: Link Rect: 410, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 412, 87, 431 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 239, 117, 246, 126 ActionDest: 526 Annotation: Subtype: Link Rect: 246, 105, 253, 113 ActionDest: 526 Annotation: Subtype: Link Rect: 256, 105, 263, 113 ActionDest: 526 Annotation: Subtype: Link Rect: 440, 92, 447, 101 ActionDest: 526 Annotation: Subtype: Link Rect: 450, 92, 457, 101 ActionDest: 526 Annotation: Subtype: Link Rect: 417, 67, 424, 76 ActionDest: 526 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 284, 735, 291, 744 ActionDest: 526 Annotation: Subtype: Link Rect: 292, 735, 304, 744 ActionDest: 529 Annotation: Subtype: Link Rect: 272, 698, 284, 707 ActionDest: 529 Annotation: Subtype: Link Rect: 414, 635, 426, 644 ActionDest: 529 Annotation: Subtype: Link Rect: 427, 635, 439, 644 ActionDest: 529 Annotation: Subtype: Link Rect: 289, 610, 301, 619 ActionDest: 529 Annotation: Subtype: Link Rect: 455, 572, 467, 581 ActionDest: 529 Annotation: Subtype: Link Rect: 467, 572, 479, 581 ActionDest: 529 Annotation: Subtype: Link Rect: 371, 547, 383, 556 ActionDest: 529 Annotation: Subtype: Link Rect: 494, 535, 506, 544 ActionDest: 529 Annotation: Subtype: Link Rect: 497, 484, 509, 493 ActionDest: 529 Annotation: Subtype: Link Rect: 275, 434, 287, 443 ActionDest: 529 Annotation: Subtype: Link Rect: 200, 384, 212, 393 ActionDest: 529 Annotation: Subtype: Link Rect: 215, 384, 227, 393 ActionDest: 529 Annotation: Subtype: Link Rect: 548, 180, 555, 192 ActionDest: 76 Annotation: Subtype: Link Rect: 511, 158, 523, 167 ActionDest: 529 Annotation: Subtype: Link Rect: 214, 133, 226, 142 ActionDest: 529 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 284, 723, 296, 732 ActionDest: 529 Annotation: Subtype: Link Rect: 440, 472, 452, 481 ActionDest: 529 Annotation: Subtype: Link Rect: 327, 459, 339, 468 ActionDest: 529 Annotation: Subtype: Link Rect: 206, 447, 218, 456 ActionDest: 529 Annotation: Subtype: Link Rect: 524, 447, 536, 456 ActionDest: 529 Annotation: Subtype: Link Rect: 212, 434, 224, 443 ActionDest: 529 Annotation: Subtype: Link Rect: 265, 434, 277, 443 ActionDest: 529 Annotation: Subtype: Link Rect: 463, 434, 475, 443 ActionDest: 529 Annotation: Subtype: Link Rect: 209, 409, 221, 418 ActionDest: 529 Annotation: Subtype: Link Rect: 282, 396, 294, 406 ActionDest: 532 Annotation: Subtype: Link Rect: 540, 371, 552, 380 ActionDest: 532 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 195, 419, 205, 427 ActionDest: 529 Annotation: Subtype: Link Rect: 461, 419, 471, 427 ActionDest: 529 Annotation: Subtype: Link Rect: 436, 377, 443, 389 ActionDest: 76 Annotation: Subtype: Link Rect: 526, 229, 538, 238 ActionDest: 532 Annotation: Subtype: Link Rect: 264, 166, 276, 175 ActionDest: 529 Annotation: Subtype: Link Rect: 272, 141, 284, 150 ActionDest: 532 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 476, 610, 488, 619 ActionDest: 532 Annotation: Subtype: Link Rect: 439, 585, 451, 594 ActionDest: 532 Annotation: Subtype: Link Rect: 224, 535, 236, 544 ActionDest: 532 Annotation: Subtype: Link Rect: 237, 535, 249, 544 ActionDest: 532 Annotation: Subtype: Link Rect: 319, 296, 331, 305 ActionDest: 532 Annotation: Subtype: Link Rect: 334, 296, 346, 305 ActionDest: 532 Annotation: Subtype: Link Rect: 483, 271, 495, 280 ActionDest: 532 Annotation: Subtype: Link Rect: 322, 221, 334, 230 ActionDest: 532 Annotation: Subtype: Link Rect: 211, 196, 223, 205 ActionDest: 532 Annotation: Subtype: Link Rect: 543, 170, 555, 180 ActionDest: 529 Annotation: Subtype: Link Rect: 301, 70, 313, 79 ActionDest: 532 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 257, 723, 269, 732 ActionDest: 532 Annotation: Subtype: Link Rect: 514, 635, 526, 644 ActionDest: 532 Annotation: Subtype: Link Rect: 205, 610, 217, 619 ActionDest: 532 Annotation: Subtype: Link Rect: 431, 560, 443, 569 ActionDest: 532 Annotation: Subtype: Link Rect: 247, 455, 254, 467 ActionDest: 76 Annotation: Subtype: Link Rect: 532, 368, 539, 380 ActionDest: 89 Annotation: Subtype: Link Rect: 292, 342, 299, 354 ActionDest: 92 Annotation: Subtype: Link Rect: 199, 330, 206, 342 ActionDest: 92 Annotation: Subtype: Link Rect: 470, 93, 480, 101 ActionDest: 529 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 234, 224, 244, 232 ActionDest: 529 Annotation: Subtype: Link Rect: 530, 224, 540, 232 ActionDest: 529 Annotation: Subtype: Link Rect: 418, 174, 425, 186 ActionDest: 116 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 182, 473, 193, 482 ActionDest: 529 Annotation: Subtype: Link Rect: 488, 473, 499, 482 ActionDest: 529 Annotation: Subtype: Link Rect: 333, 372, 340, 385 ActionDest: 116 Annotation: Subtype: Link Rect: 440, 335, 447, 347 ActionDest: 116 Annotation: Subtype: Link Rect: 405, 148, 415, 155 ActionDest: 529 Annotation: Subtype: Link Rect: 262, 107, 269, 119 ActionDest: 116 Annotation: Subtype: Link Rect: 371, 57, 378, 69 ActionDest: 116 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 288, 708, 295, 720 ActionDest: 116 Annotation: Subtype: Link Rect: 217, 670, 223, 682 ActionDest: 146 Annotation: Subtype: Link Rect: 365, 657, 372, 669 ActionDest: 169 Annotation: Subtype: Link Rect: 233, 632, 240, 644 ActionDest: 295 Annotation: Subtype: Link Rect: 304, 619, 311, 631 ActionDest: 295 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 346, 126, 357, 134 ActionDest: 529 Page: Sequence: 12 Page: Sequence: 13 Page: Sequence: 14 Page: Sequence: 15 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 371, 632, 378, 644 ActionDest: 295 Annotation: Subtype: Link Rect: 463, 595, 470, 607 ActionDest: 295 Annotation: Subtype: Link Rect: 438, 507, 445, 519 ActionDest: 76 Annotation: Subtype: Link Rect: 216, 494, 223, 506 ActionDest: 332 Annotation: Subtype: Link Rect: 266, 494, 273, 506 ActionDest: 371 Annotation: Subtype: Link Rect: 543, 63, 554, 72 ActionDest: 529 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 200, 477, 210, 485 ActionDest: 529 Annotation: Subtype: Link Rect: 357, 448, 364, 460 ActionDest: 371 Annotation: Subtype: Link Rect: 410, 448, 417, 460 ActionDest: 414 Annotation: Subtype: Link Rect: 346, 108, 357, 116 ActionDest: 529 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 200, 513, 210, 521 ActionDest: 529 Annotation: Subtype: Link Rect: 265, 384, 272, 396 ActionDest: 414 Annotation: Subtype: Link Rect: 356, 296, 362, 308 ActionDest: 417 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 201, 621, 211, 629 ActionDest: 529 Annotation: Subtype: Link Rect: 540, 570, 550, 577 ActionDest: 529 Annotation: Subtype: Link Rect: 402, 297, 412, 304 ActionDest: 529 Annotation: Subtype: Link Rect: 418, 222, 425, 234 ActionDest: 414 Annotation: Subtype: Link Rect: 299, 185, 306, 197 ActionDest: 420 Annotation: Subtype: Link Rect: 527, 97, 534, 109 ActionDest: 420 Annotation: Subtype: Link Rect: 190, 84, 197, 96 ActionDest: 420 Annotation: Subtype: Link Rect: 395, 84, 402, 96 ActionDest: 414 Page: Sequence: 20 Annotations: Annotation: Subtype: Link Rect: 492, 417, 503, 425 ActionDest: 529 Annotation: Subtype: Link Rect: 539, 112, 549, 119 ActionDest: 529 Page: Sequence: 21 Annotations: Annotation: Subtype: Link Rect: 492, 733, 499, 745 ActionDest: 501 Annotation: Subtype: Link Rect: 322, 695, 329, 707 ActionDest: 414 Annotation: Subtype: Link Rect: 200, 523, 210, 531 ActionDest: 529 Annotation: Subtype: Link Rect: 282, 504, 292, 511 ActionDest: 529 Annotation: Subtype: Link Rect: 327, 436, 334, 448 ActionDest: 414 Annotation: Subtype: Link Rect: 552, 285, 559, 297 ActionDest: 76 Annotation: Subtype: Link Rect: 431, 262, 443, 271 ActionDest: 532 Annotation: Subtype: Link Rect: 444, 262, 456, 271 ActionDest: 532 Annotation: Subtype: Link Rect: 473, 250, 485, 259 ActionDest: 532 Annotation: Subtype: Link Rect: 315, 225, 322, 234 ActionDest: 526 Annotation: Subtype: Link Rect: 499, 200, 506, 208 ActionDest: 526 Annotation: Subtype: Link Rect: 512, 174, 524, 183 ActionDest: 532 Annotation: Subtype: Link Rect: 524, 174, 536, 183 ActionDest: 532 Annotation: Subtype: Link Rect: 520, 149, 532, 158 ActionDest: 532 Annotation: Subtype: Link Rect: 475, 137, 487, 146 ActionDest: 529 Annotation: Subtype: Link Rect: 523, 99, 535, 108 ActionDest: 532 Annotation: Subtype: Link Rect: 335, 87, 342, 96 ActionDest: 526 Annotation: Subtype: Link Rect: 342, 86, 354, 96 ActionDest: 529 Annotation: Subtype: Link Rect: 355, 86, 367, 96 ActionDest: 532 Page: Sequence: 22 Annotations: Annotation: Subtype: Link Rect: 221, 735, 233, 744 ActionDest: 532 Annotation: Subtype: Link Rect: 379, 698, 391, 707 ActionDest: 532 Annotation: Subtype: Link Rect: 392, 698, 403, 707 ActionDest: 532 Annotation: Subtype: Link Rect: 414, 685, 426, 694 ActionDest: 532 Annotation: Subtype: Link Rect: 260, 635, 272, 644 ActionDest: 529 Annotation: Subtype: Link Rect: 272, 635, 284, 644 ActionDest: 529 Annotation: Subtype: Link Rect: 285, 635, 297, 644 ActionDest: 532 Annotation: Subtype: Link Rect: 339, 635, 351, 644 ActionDest: 536 Annotation: Subtype: Link Rect: 454, 635, 466, 644 ActionDest: 532 Annotation: Subtype: Link Rect: 375, 582, 382, 594 ActionDest: 116 Annotation: Subtype: Link Rect: 249, 459, 261, 468 ActionDest: 536 Annotation: Subtype: Link Rect: 229, 434, 240, 443 ActionDest: 529 Annotation: Subtype: Link Rect: 267, 233, 279, 242 ActionDest: 536 Annotation: Subtype: Link Rect: 271, 145, 283, 154 ActionDest: 536 Annotation: Subtype: Link Rect: 214, 95, 226, 104 ActionDest: 536 Page: Sequence: 23 Annotations: Annotation: Subtype: Link Rect: 543, 647, 555, 657 ActionDest: 536 Annotation: Subtype: Link Rect: 479, 635, 491, 644 ActionDest: 532 Annotation: Subtype: Link Rect: 269, 622, 281, 631 ActionDest: 536 Annotation: Subtype: Link Rect: 410, 595, 417, 607 ActionDest: 295 Annotation: Subtype: Link Rect: 194, 258, 206, 267 ActionDest: 529 Annotation: Subtype: Link Rect: 253, 246, 265, 255 ActionDest: 536 Annotation: Subtype: Link Rect: 349, 208, 361, 217 ActionDest: 536 Annotation: Subtype: Link Rect: 194, 82, 201, 91 ActionDest: 526 Annotation: Subtype: Link Rect: 201, 82, 208, 91 ActionDest: 526 Annotation: Subtype: Link Rect: 209, 82, 221, 91 ActionDest: 529 Annotation: Subtype: Link Rect: 221, 82, 233, 91 ActionDest: 532 Annotation: Subtype: Link Rect: 234, 82, 246, 91 ActionDest: 536 Annotation: Subtype: Link Rect: 246, 82, 258, 91 ActionDest: 536 Annotation: Subtype: Link Rect: 259, 82, 271, 91 ActionDest: 536 Annotation: Subtype: Link Rect: 274, 82, 286, 91 ActionDest: 536 Annotation: Subtype: Link Rect: 498, 82, 510, 91 ActionDest: 536 Page: Sequence: 24 Annotations: Annotation: Subtype: Link Rect: 234, 735, 246, 744 ActionDest: 536 Annotation: Subtype: Link Rect: 480, 660, 492, 669 ActionDest: 532 Annotation: Subtype: Link Rect: 242, 595, 254, 607 ActionDest: 511 Annotation: Subtype: Link Rect: 194, 507, 206, 519 ActionDest: 511 Annotation: Subtype: Link Rect: 373, 497, 380, 506 ActionDest: 526 Annotation: Subtype: Link Rect: 381, 497, 393, 506 ActionDest: 536 Annotation: Subtype: Link Rect: 203, 246, 213, 254 ActionDest: 529 Annotation: Subtype: Link Rect: 301, 237, 311, 244 ActionDest: 532 Annotation: Subtype: Link Rect: 422, 187, 432, 195 ActionDest: 529 Annotation: Subtype: Link Rect: 411, 133, 423, 145 ActionDest: 511 Page: Sequence: 25 Annotations: Annotation: Subtype: Link Rect: 453, 723, 465, 732 ActionDest: 532 Annotation: Subtype: Link Rect: 328, 381, 335, 393 ActionDest: 417 Annotation: Subtype: Link Rect: 509, 371, 521, 380 ActionDest: 536 Annotation: Subtype: Link Rect: 210, 334, 222, 343 ActionDest: 536 Annotation: Subtype: Link Rect: 454, 309, 466, 318 ActionDest: 536 Annotation: Subtype: Link Rect: 427, 208, 439, 217 ActionDest: 536 Annotation: Subtype: Link Rect: 378, 93, 385, 105 ActionDest: 420 Page: Sequence: 26 Annotations: Annotation: Subtype: Link Rect: 476, 673, 488, 682 ActionDest: 532 Annotation: Subtype: Link Rect: 525, 645, 532, 657 ActionDest: 414 Annotation: Subtype: Link Rect: 340, 635, 352, 644 ActionDest: 536 Annotation: Subtype: Link Rect: 280, 622, 292, 631 ActionDest: 529 Annotation: Subtype: Link Rect: 427, 356, 438, 365 ActionDest: 536 Annotation: Subtype: Link Rect: 294, 343, 306, 352 ActionDest: 536 Annotation: Subtype: Link Rect: 310, 306, 322, 315 ActionDest: 536 Annotation: Subtype: Link Rect: 548, 278, 555, 290 ActionDest: 76 Annotation: Subtype: Link Rect: 512, 142, 524, 151 ActionDest: 532 Page: Sequence: 27 Annotations: Annotation: Subtype: Link Rect: 165, 456, 410, 467 Page: Sequence: 28 Page: Sequence: 29 Annotations: Annotation: Subtype: Link Rect: 108, 330, 146, 340 Annotation: Subtype: Link Rect: 152, 330, 188, 340 Annotation: Subtype: Link Rect: 59, 307, 96, 317 Annotation: Subtype: Link Rect: 375, 283, 412, 294 Annotation: Subtype: Link Rect: 418, 283, 454, 294 Annotation: Subtype: Link Rect: 268, 249, 306, 260 Annotation: Subtype: Link Rect: 312, 249, 348, 260 Annotation: Subtype: Link Rect: 331, 226, 368, 237 Annotation: Subtype: Link Rect: 283, 191, 320, 202 Annotation: Subtype: Link Rect: 381, 157, 418, 168 Annotation: Subtype: Link Rect: 201, 134, 239, 144 Annotation: Subtype: Link Rect: 59, 88, 96, 98 Page: Sequence: 30 Annotations: Annotation: Subtype: Link Rect: 193, 711, 231, 721 Annotation: Subtype: Link Rect: 270, 676, 307, 687 Annotation: Subtype: Link Rect: 59, 642, 96, 652 Annotation: Subtype: Link Rect: 248, 607, 285, 617 Annotation: Subtype: Link Rect: 56, 560, 163, 571 Annotation: Subtype: Link Rect: 316, 537, 353, 548 Annotation: Subtype: Link Rect: 327, 514, 364, 525 Annotation: Subtype: Link Rect: 371, 514, 407, 525 Annotation: Subtype: Link Rect: 519, 503, 557, 514 Annotation: Subtype: Link Rect: 424, 480, 462, 491 Annotation: Subtype: Link Rect: 299, 445, 336, 456 Annotation: Subtype: Link Rect: 59, 400, 96, 410 Annotation: Subtype: Link Rect: 102, 400, 138, 410 Annotation: Subtype: Link Rect: 195, 366, 232, 376 Annotation: Subtype: Link Rect: 239, 366, 275, 376 Annotation: Subtype: Link Rect: 441, 330, 478, 341 Annotation: Subtype: Link Rect: 484, 330, 520, 341 Annotation: Subtype: Link Rect: 240, 297, 278, 307 Annotation: Subtype: Link Rect: 284, 297, 320, 307 Annotation: Subtype: Link Rect: 301, 261, 338, 272 Annotation: Subtype: Link Rect: 81, 239, 119, 249 Annotation: Subtype: Link Rect: 125, 239, 161, 249 Annotation: Subtype: Link Rect: 347, 204, 560, 215 Annotation: Subtype: Link Rect: 56, 193, 100, 203 Annotation: Subtype: Link Rect: 332, 181, 432, 192 Annotation: Subtype: Link Rect: 316, 169, 509, 180 Annotation: Subtype: Link Rect: 354, 146, 436, 157 Annotation: Subtype: Link Rect: 332, 135, 434, 146 Annotation: Subtype: Link Rect: 86, 100, 193, 111 Annotation: Subtype: Link Rect: 301, 89, 429, 100 Annotation: Subtype: Link Rect: 312, 77, 438, 88 Page: Sequence: 31 Annotations: Annotation: Subtype: Link Rect: 56, 722, 216, 733 Annotation: Subtype: Link Rect: 273, 710, 560, 721 Annotation: Subtype: Link Rect: 109, 665, 146, 675 Annotation: Subtype: Link Rect: 152, 665, 188, 675 Annotation: Subtype: Link Rect: 364, 641, 560, 652 Annotation: Subtype: Link Rect: 56, 629, 71, 640 Annotation: Subtype: Link Rect: 152, 584, 190, 594 Annotation: Subtype: Link Rect: 426, 572, 560, 583 Annotation: Subtype: Link Rect: 56, 560, 99, 571 Annotation: Subtype: Link Rect: 520, 537, 557, 548 Annotation: Subtype: Link Rect: 59, 527, 95, 537 Annotation: Subtype: Link Rect: 355, 504, 392, 514 Annotation: Subtype: Link Rect: 108, 469, 146, 479 Annotation: Subtype: Link Rect: 425, 435, 463, 445 Annotation: Subtype: Link Rect: 520, 422, 557, 433 Annotation: Subtype: Link Rect: 319, 411, 356, 422 Annotation: Subtype: Link Rect: 362, 411, 398, 422 Annotation: Subtype: Link Rect: 117, 377, 155, 387 Annotation: Subtype: Link Rect: 161, 377, 197, 387 Annotation: Subtype: Link Rect: 421, 353, 459, 364 Annotation: Subtype: Link Rect: 218, 330, 375, 341 Annotation: Subtype: Link Rect: 507, 330, 544, 341 Annotation: Subtype: Link Rect: 327, 296, 364, 307 Annotation: Subtype: Link Rect: 100, 262, 137, 272 Annotation: Subtype: Link Rect: 143, 262, 179, 272 Annotation: Subtype: Link Rect: 263, 227, 300, 238 Annotation: Subtype: Link Rect: 536, 215, 560, 226 Annotation: Subtype: Link Rect: 56, 204, 248, 215 Annotation: Subtype: Link Rect: 127, 182, 164, 192 Annotation: Subtype: Link Rect: 450, 158, 487, 169 Annotation: Subtype: Link Rect: 364, 135, 401, 146 Annotation: Subtype: Link Rect: 246, 112, 284, 123 Annotation: Subtype: Link Rect: 290, 112, 326, 123 Annotation: Subtype: Link Rect: 109, 90, 146, 100 Annotation: Subtype: Link Rect: 152, 90, 188, 100 Annotation: Subtype: Link Rect: 481, 66, 518, 77 Page: Sequence: 32 Annotations: Annotation: Subtype: Link Rect: 434, 722, 472, 733 Annotation: Subtype: Link Rect: 478, 722, 514, 733 Annotation: Subtype: Link Rect: 323, 699, 360, 710 Annotation: Subtype: Link Rect: 366, 699, 402, 710 Annotation: Subtype: Link Rect: 129, 665, 166, 675 Annotation: Subtype: Link Rect: 272, 629, 309, 640 Annotation: Subtype: Link Rect: 390, 606, 560, 617 Annotation: Subtype: Link Rect: 56, 595, 224, 606 Annotation: Subtype: Link Rect: 238, 573, 275, 583 Annotation: Subtype: Link Rect: 100, 538, 137, 548 Annotation: Subtype: Link Rect: 321, 503, 359, 514 Annotation: Subtype: Link Rect: 247, 469, 285, 479 Annotation: Subtype: Link Rect: 498, 445, 536, 456 Annotation: Subtype: Link Rect: 320, 422, 358, 433 Annotation: Subtype: Link Rect: 185, 400, 222, 410 Annotation: Subtype: Link Rect: 248, 376, 560, 387 Annotation: Subtype: Link Rect: 520, 342, 557, 353 Annotation: Subtype: Link Rect: 384, 307, 421, 318 Checksum: 3753c808 Type: CRC32 Checksum: 066c02b7f6ba7182e5edadfc40706d5a Type: MD5 Checksum: c79af106cc8a512a7aa1ac9c59c24d3351be9c73 Type: SHA-1 Checksum: 151d5d081dbc23bab27e29b3f175b9ee5d69783d9e9d6560f844f256e9e1770c Type: SHA-256